Reduced-order modeling of light transport in tissue for real-time monitoring of brain hemodynamics using diffuse optical tomography

This paper proposes a new reconstruction method for diffuse optical tomography using reduced-order models of light transport in tissue. The models, which directly map optical tissue parameters to optical flux measurements at the detector locations, are derived based on data generated by numerical simulation of a reference model. The reconstruction algorithm based on the reduced-order models is a few orders of magnitude faster than the one based on a finite element approximation on a fine mesh incorporating a priori anatomical information acquired by magnetic resonance imaging. We demonstrate the accuracy and speed of the approach using a phantom experiment and through numerical simulation of brain activation in a rat's head. The applicability of the approach for real-time monitoring of brain hemodynamics is demonstrated through a hypercapnic experiment. We show that our results agree with the expected physiological changes and with results of a similar experimental study. However, by using our approach, a three-dimensional tomographic reconstruction can be performed in ∼3  s per time point instead of the 1 to 2 h it takes when using the conventional finite element modeling approach

Reduced neural response to reward following 7 days treatment with the cannabinoid CB1 antagonist rimonabant in healthy volunteers

Reduced subjective experience of reward (anhedonia) is a key symptom of major depression. The anti-obesity drug and cannabinoid type 1 receptor (CB(1)) antagonist, rimonabant, is associated with significant rates of depression and anxiety in clinical use and was recently withdrawn from the market because of these adverse effects. Using a functional magnetic resonance imaging (fMRI) model of reward we hypothesized that rimonabant would impair reward processing. Twenty-two healthy participants were randomly allocated to receive rimonabant (20 mg), or placebo, for 7 d in a double-blind, parallel group design. We used fMRI to measure the neural response to rewarding (sight and/or flavour of chocolate) and aversive (sight of mouldy strawberries and/or an unpleasant strawberry taste) stimuli on the final day of drug treatment. Rimonabant reduced the neural response to chocolate stimuli in key reward areas such as the ventral striatum and the orbitofrontal cortex. Rimonabant also decreased neural responses to the aversive stimulus condition in the caudate nucleus and ventral striatum, but increased lateral orbitofrontal activations to the aversive sight and taste of strawberry condition. Our findings are the first to show that the anti-obesity drug rimonabant inhibits the neural processing of rewarding food stimuli in humans. This plausibly underlies its ability to promote weight loss, but may also indicate a mechanism for inducing anhedonia which could lead to the increased risk of depressive symptomatology seen in clinical use. fMRI may be a useful method of screening novel agents for unwanted effects on reward and associated clinical adverse reactions.

The extent to which potential benefits to EU farmers of adopting transgenic crops are reduced by cost of compliance with coexistence regulations

This article forecasts the extent to which the potential benefits of adopting transgenic crops may be reduced by costs of compliance with coexistence regulations applicable in various member states of the EU. A dynamic economic model is described and used to calculate the potential yield and gross margin of a set of crops grown in a selection of typical rotation scenarios. The model simulates varying levels of pest, weed, and drought pressures, with associated management strategies regarding pesticide and herbicide application, and irrigation. We report on the initial use of the model to calculate the net reduction in gross margin attributable to coexistence costs for insect-resistant (IR) and herbicide-tolerant (HT) maize grown continuously or in a rotation, HT soya grown in a rotation, HT oilseed rape grown in a rotation, and HT sugarbeet grown in a rotation. Conclusions are drawn about conditions favoring inclusion of a transgenic crop in a crop rotation, having regard to farmers’ attitude toward risk.

Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions

Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative RT-PCR confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher relative fitness compared to wild-type virus, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during positive-stranded RNA virus infection.

The physics of orographic gravity wave drag

The drag and momentum fluxes produced by gravity waves generated in flow over orography are reviewed, focusing on adiabatic conditions without phase transitions or radiation effects, and steady mean incoming flow. The orographic gravity wave drag is first introduced in its simplest possible form, for inviscid, linearized, non-rotating flow with the Boussinesq and hydrostatic approximations, and constant wind and static stability. Subsequently, the contributions made by previous authors (primarily using theory and numerical simulations) to elucidate how the drag is affected by additional physical processes are surveyed. These include the effect of orography anisotropy, vertical wind shear, total and partial critical levels, vertical wave reflection and resonance, non-hydrostatic effects and trapped lee waves, rotation and nonlinearity. Frictional and boundary layer effects are also briefly mentioned. A better understanding of all of these aspects is important for guiding the improvement of drag parametrization schemes.

Compensation between resolved wave driving and parameterized orographic gravity wave driving of the Brewer–Dobson circulation and its response to climate change

Following recent findings, the interaction between resolved (Rossby) wave drag and parameterized orographic gravity wave drag (OGWD) is investigated, in terms of their driving of the Brewer–Dobson circulation (BDC), in a comprehensive climate model. To this end, the parameter that effectively determines the strength of OGWD in present-day and doubled CO2 simulations is varied. The authors focus on the Northern Hemisphere during winter when the largest response of the BDC to climate change is predicted to occur. It is found that increases in OGWD are to a remarkable degree compensated by a reduction in midlatitude resolved wave drag, thereby reducing the impact of changes in OGWD on the BDC. This compensation is also found for the response to climate change: changes in the OGWD contribution to the BDC response to climate change are compensated by opposite changes in the resolved wave drag contribution to the BDC response to climate change, thereby reducing the impact of changes in OGWD on the BDC response to climate change. By contrast, compensation does not occur at northern high latitudes, where resolved wave driving and the associated downwelling increase with increasing OGWD, both for the present-day climate and the response to climate change. These findings raise confidence in the credibility of climate model projections of the strengthened BDC.

Curl free pressure gradients over orography in a solution of the fully compressible Euler equations with implicit treatment of acoustic and gravity waves

Steep orography can cause noisy solutions and instability in models of the atmosphere. A new technique for modelling flow over orography is introduced which guarantees curl free gradients on arbitrary grids, implying that the pressure gradient term is not a spurious source of vorticity. This mimetic property leads to better hydrostatic balance and better energy conservation on test cases using terrain following grids. Curl-free gradients are achieved by using the co-variant components of velocity over orography rather than the usual horizontal and vertical components. In addition, gravity and acoustic waves are treated implicitly without the need for mean and perturbation variables or a hydrostatic reference profile. This enables a straightforward description of the implicit treatment of gravity waves. Results are presented of a resting atmosphere over orography and the curl-free pressure gradient formulation is advantageous. Results of gravity waves over orography are insensitive to the placement of terrain-following layers. The model with implicit gravity waves is stable in strongly stratified conditions, with N∆t up to at least 10 (where N is the Brunt-V ̈ais ̈al ̈a frequency). A warm bubble rising over orography is simulated and the curl free pressure gradient formulation gives much more accurate results for this test case than a model without this mimetic property.

Effects of a mid-latitude solar eclipse on the thermosphere and ionosphere: a modelling study

A modelling study is presented which investigates in-situ generated changes of the thermosphere and ionosphere during a solar eclipse. Neutral temperatures are expected to drop by up to 40 degrees K at 240 km height in the totality footprint, with neutral winds of up to 26 m/s responding to the change of pressure. Both temperatures and winds are found to respond with a time lag of 30 min after the passing of the Moon's shadow. A gravity wave is generated in the neutral atmosphere and propagates into the opposite hemisphere at around 300 m/s. The combined effects of thermal cooling and downwelling lead to an overall increase in [O], while [N(2)] initially rises and then for several hours after the eclipse is below the "steady state" level. An enhancement of [NmF2] is found and explained by the atmosphere's contraction during, and the reduced [O]/[N(2)] ratio after the eclipse.

Sensory profiles and consumer acceptability of a range of sugar-reduced products on the UK market

Current UK intake of non-milk extrinsic sugars (NMES) is above recommendations. Reducing the sugar content of processed high sugar foods through reformulation is one option for reducing consumption of NMES at a population level. However, reformulation can alter the sensory attributes of food products and influence consumer liking. This study evaluated consumer acceptance of a selection of products that are commercially-available in the UK; these included regular and sugar-reduced baked beans, strawberry jam, milk chocolate, cola and cranberry & raspberry juice. Sweeteners were present in the reformulated chocolate (maltitol), cola (aspartame and acesulfame-K) and juice (sucralose) samples. Healthy, non-smoking consumers (n = 116; 55 men, 61 women, age: 33 ± 9 years; BMI: 25.7 ± 4.6 kg/m2) rated the products for overall liking and on liking of appearance, flavor and texture using a nine-point hedonic scale. There were significant differences between standard and reduced sugar products in consumers’ overall liking and on liking of each modality (appearance, flavor and texture; all P < 0.0001). For overall liking, only the regular beans and cola were significantly more liked than their reformulated counterparts (P < 0.0001). Cluster analysis identified three consumer clusters that were representative of different patterns of consumer liking. For the largest cluster (cluster 3: 45%), there was a significant difference in mean liking scores across all products, except jam. Differences in liking were predominantly driven by sweet taste in 2 out of 3 clusters. The current research has demonstrated that a high proportion of consumers prefer conventional products over sugar-reduced products across a wide range of product types (45%) or across selected products (27%), when tasted unbranded, and so there is room for further optimization of commercial reduced sugar products that were evaluated in the current study. Future work should evaluate strategies to facilitate compliance to dietary recommendations on NMES and free sugars, such as the impact of sugar-reduced food exposure on their acceptance.

The persistence of distance: a gravity model of European cross-border real estate development flows

Purpose – This paper aims to investigate the scale and drivers of cross-border real estate development in Western Europe and Central and Eastern Europe. Design/methodology/approach – Placing cross-border real estate development within the framework of foreign direct investment (FDI), conceptual complexities in characterizing the notional real estate developer are emphasized. Drawing upon a transaction database, this paper proxies cross-border real estate development flows with asset sales by developers. Findings – Much higher levels of market penetration by international real estate developers are found in the less mature markets of Central and Eastern Europe. Analysis suggests a complex range of determinants with physical distance remaining a consistent barrier to cross-border development flows. Originality/value – This analysis adds significant value in terms of understanding cross-border real estate development flows. In this study, a detailed examination of the issues based on a rigorous empirical analysis through gravity modelling is offered. The gravity framework is one of the most confirmed empirical regularities in international economics and commonly applied to trade, FDI, migration, foreign portfolio investment inter alia. This paper assesses the extent to which it provides useful insights into the pattern of cross-border real estate development flows.

Reduced face preference in infancy: a developmental precursor to callous-unemotional traits?

Background Children with callous-unemotional (CU) traits, a proposed precursor to adult psychopathy, are characterized by impaired emotion recognition, reduced responsiveness to others’ distress, and a lack of guilt or empathy. Reduced attention to faces, and more specifically to the eye region, has been proposed to underlie these difficulties, although this has never been tested longitudinally from infancy. Attention to faces occurs within the context of dyadic caregiver interactions, and early environment including parenting characteristics has been associated with CU traits. The present study tested whether infants’ preferential tracking of a face with direct gaze and levels of maternal sensitivity predict later CU traits. Methods Data were analyzed from a stratified random sample of 213 participants drawn from a population-based sample of 1233 first-time mothers. Infants’ preferential face tracking at 5 weeks and maternal sensitivity at 29 weeks were entered into a weighted linear regression as predictors of CU traits at 2.5 years. Results Controlling for a range of confounders (e.g., deprivation), lower preferential face tracking predicted higher CU traits (p = .001). Higher maternal sensitivity predicted lower CU traits in girls (p = .009), but not boys. No significant interaction between face tracking and maternal sensitivity was found. Conclusions This is the first study to show that attention to social features during infancy as well as early sensitive parenting predict the subsequent development of CU traits. Identifying such early atypicalities offers the potential for developing parent-mediated interventions in children at risk for developing CU traits.

Energy compensation following consumption of sugar-reduced products: a randomized controlled trial

PURPOSE: Consumption of sugar-reformulated products (commercially available foods and beverages that have been reduced in sugar content through reformulation) is a potential strategy for lowering sugar intake at a population level. The impact of sugar-reformulated products on body weight, energy balance (EB) dynamics and cardiovascular disease risk indicators has yet to be established. The REFORMulated foods (REFORM) study examined the impact of an 8-week sugar-reformulated product exchange on body weight, EB dynamics, blood pressure, arterial stiffness, glycemia and lipemia. METHODS: A randomized, controlled, double-blind, crossover dietary intervention study was performed with fifty healthy normal to overweight men and women (age 32.0 ± 9.8 year, BMI 23.5 ± 3.0 kg/m2) who were randomly assigned to consume either regular sugar or sugar-reduced foods and beverages for 8 weeks, separated by 4-week washout period. Body weight, energy intake (EI), energy expenditure and vascular markers were assessed at baseline and after both interventions. RESULTS: We found that carbohydrate (P < 0.001), total sugars (P < 0.001) and non-milk extrinsic sugars (P < 0.001) (% EI) were lower, whereas fat (P = 0.001) and protein (P = 0.038) intakes (% EI) were higher on the sugar-reduced than the regular diet. No effects on body weight, blood pressure, arterial stiffness, fasting glycemia or lipemia were observed. CONCLUSIONS: Consumption of sugar-reduced products, as part of a blinded dietary exchange for an 8-week period, resulted in a significant reduction in sugar intake. Body weight did not change significantly, which we propose was due to energy compensation.

Reduced relative entropy techniques for a posteriori analysis of multiphase problems in elastodynamics

We give an a posteriori analysis of a semidiscrete discontinuous Galerkin scheme approximating solutions to a model of multiphase elastodynamics, which involves an energy density depending not only on the strain but also the strain gradient. A key component in the analysis is the reduced relative entropy stability framework developed in Giesselmann (2014, SIAM J. Math. Anal., 46, 3518–3539). This framework allows energy-type arguments to be applied to continuous functions. Since we advocate the use of discontinuous Galerkin methods we make use of two families of reconstructions, one set of discrete reconstructions and a set of elliptic reconstructions to apply the reduced relative entropy framework in this setting.

Reduced relative entropy techniques for a priori analysis of multiphase problems in elastodynamics

We give an a priori analysis of a semi-discrete discontinuous Galerkin scheme approximating solutions to a model of multiphase elastodynamics which involves an energy density depending not only on the strain but also the strain gradient. A key component in the analysis is the reduced relative entropy stability framework developed in Giesselmann (SIAM J Math Anal 46(5):3518–3539, 2014). The estimate we derive is optimal in the L∞(0,T;dG) norm for the strain and the L2(0,T;dG) norm for the velocity, where dG is an appropriate mesh dependent H1-like space.